Anti-vascular endothelial growth factor antibody bevacizumab reduced the risk of anemia associated with chemotherapy–A meta-analysis

Figures & data

Table I. National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Versions 2 and 3 for anemia.

	Version 2 (g/dL)	Version 3 (g/dL)
0 (normal)	WNL	WNL
1 (mild)	10.0 to < LLN	10.0 to < LLN
2 (moderate)	8.0 to < 10.0	8.0 to < 10.0
3 (severe)	6.5 to < 8.0	6.5 to < 8.0
4 (life-threatening)	< 6.5	< 6.5
5 (death)	None	Death

Notes and abbreviations: WNL, within normal limits; LLN, lower limit of normal.

Figure 1. Selection process for randomized clinical trials included in the meta-analysis.

Table II. Characteristics of randomized controlled trials included in the meta-analysis.

Study name	Trial phase	No. enrolled	No. for analysis	Duration of follow-up, median (range), mo	Underlying malignancy	Concurrent treatment	Bevacizumab dose, mg/kg per wk(a)
Escudier et al. [22] 2007	3	649	641	13.3 (0–25.6)	Renal cell carcinoma	Interferon alfa	5
Herbst et al. [28] 2007	2	122	78	15.8 (NA)	NSCLC-NSQ	Docetaxel or pemetrexed	5
Karrison et al. [23] 2007	2	115	108	15.1 (NA)	Mesothelioma	Cisplatin and gemcitabine	5
Kindler et al. [24] 2007	3	602	540	11.3 (NA)	Pancreatic cancer	Gemcitabine	5
Miles et al. [25] 2008	3	736	730	10.2 (0–17.5)	Breast cancer	Docetaxel	2.5 or 5
Miller et al. [30] 2005	3	462	444	14.8 (NA)	Breast cancer	Capecitabine	5
Miller et al. [31] 2007	3	722	711	25.9 (NA)	Breast cancer	Paclitaxel	5
Reck et al. [27] 2009	3	1043	986	NA	NSCLC-NSQ	Cisplatin and gemcitabine	2.5 or 5
Rini et al. [33] 2010	3	732	715	NA	Renal cell carcinoma	Interferon alfa	5
Sandler et al. [29] 2006	3	878	867	19.0 (NA)	NSCLC-NSQ	Paclitaxel and carboplatin	5
Van Cutsem et al. [26] 2009	3	607	583	6.7 (NA)	Pancreatic cancer	Gemcitabine and erlotinib	2.5

NA, data not available; NSCLC, non-small cell lung carcinoma; NSQ, non-squamous cell cancer.

Funding sources: Three trials were sponsored by Genentech [28,30,31]. Four trials were supported by Hoffman-La Roche [22,25–27]. Four trials were supported in part by the National Cancer Institute and the National Institutes of Health [24,29,31–33] One trial was supported by Mesothelioma Applied Research Foundation [23]. (a) The dose schedule was converted from mg/kg per schedule.

Figure 2. Relative risk (RR) of anemia with bevacizumab compared with control. Both fixed- and random-effects models were used to calculate relative risks. Overall relative risks of all-grade (A) and high-grade (B) anemia were reported using the random and fixed -effects models. The incidence of anemia was compared between patients treated with bevacizumab in combination with chemotherapy (bevacizumab) and chemotherapy alone (control) in each study. RR for each study is displayed numerically on the left and graphically on the right. Total events and sample sizes are also displayed for each study. For study name, the first author's name was used to represent each trial. If the same first author was involved in two trials, then the publication year was also included to identify the trial. For each trial the position of the square denoted the value of RR, horizontal lines represent 95% CI, and diamond plot represents overall results of the included trials.

Table III. Incidence and relative risk (RR) of high-grade anemia with bevacizumab among patients with various tumor types.

	No. of studies	High-grade anemia (no./total no.) bevacizumab	High-grade anemia (no./total no.) control	Incidence (95% CI), %	RR (95% CI)
Overall	11	139/3580	140/2859	2.9 (1.6–5.0)	0.72 (0.57–0.90)
Breast cancer	3	9/1091	7/794	0.9 (0.4–2.2)	1.1 (0.18–7.0)
Lung cancer	3	70/1164	48/809	2.3 (0.3–1.5)	0.73 (0.32–1.67)
Renal cell carcinoma	2	23/699	30/651	3.3 (2.2–4.9)	0.71 (0.34–1.5)
Pancreatic cancer	2	35/573	47/550	6.2 (4.4–8.5)	0.72 (0.47–1.09)
Mesothelioma	1	2/53	8/55	3.8 (0.9–13.9)	0.26 (0.06–1.17)

CI, confidence interval. The incidence and RR were calculated from the trials included in this study by meta-analysis as described in the “Methods” section.

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